The CD3/TCR (T cell antigen receptor) complex on the surface of T cells not only recognizes nonself antigen (Ag) in the context of self major histocompatibility (MHC) molecules expressed on the surface of antigen presenting cells (APC) but also participates in signal transduction to initiate the activation of T cells (Clevers H. et al. (1988) Ann. Rev. Immuno. 6: 629). The interaction between CD3/TCR and Ag/MHC on APC, although essential to initiate the activation of T cells, is usually not sufficient and requires participation of additional cell-surface molecules which mediate adhesion and/or signal transduction for optimal expression of various functions of activated T cells (Clevers H. et al. (1988) Ann. Rev. Immuno. 6: 629; Springer T. A. (1990) Nature 346: 425; Moller G. (1990) Immunol. Rev. 114: 1-217).
The leukocyte adhesion molecule LFA-1 (CD11a/CD18) expressed on the surface of all mature leukocytes mediates a wide range of interactions with other somatic cells during the immune response and inflammation by interaction with its ligand the intercellular adhesion molecule-1 (ICAM-1/CD54) (Springer T. A. (1990) Nature 346: 425; Moller G. (1990); Moller G. (1990) Immunol. Rev. 114: 217; Kishimoto T. K. et al. (1989) Adv. Immunol. 46: 149; Marlin S. D. et al. (1987) Cell 51: 813; Makgoba M. W. et al. (1988) Nature 331: 86; Staunton D. E. et al. (1988) Cell 52: 925; Simmons, D. et al. (1988) Nature 331: 624; Staunton D. E. et al. (1990) Cell 61: 243; Boyd A. W. et al. (1988) Proc. Natl. Acad. Sci. USA 85: 3095; Dougherty, G. et al. (1988) Eur. J. Immunol. 18: 35; Altmann D. M. et al. (1989) Nature 338: 512). ICAM-1 is constitutively expressed on some tissues and induced on others during inflammation (Dustin M. L. et al. (1986) J. Immunol. 137: 245). ICAM-1 provides an important costimulatory signal via its adhesive interaction with LFA-1 during the CD3/TCR-mediated activation of resting T cells (Van Seventer G. A. et al. (1990) J. Immunol. 144: 4579). Recently, another ligand for LFA-1, ICAM-2 has been identified which can mediate the ICAM-1 independent adhesion of LFA-1.sup.+ cells (Staunton D. E. et al. (1989) Nature 339: 61; Dustin M. L. et al. (1989) Cold Spring Harbor Symp. Quant. Biol. 54: 753). Expression of ICAM-2 is restricted and is not readily upregulated with proinflammatory stimuli (De Fougerolles A. R. et al. (1991) J. Exp. Med. 174: 253; Nortamo, P. et al. (1991) J. Immunol. 146: 2530).
In the present invention soluble recombinant ICAM-1 and ICAM-2 immunoglobulin fusion proteins have been created to analyze and compare the roles of these molecules in cellular interactions underlying various immune responses. This invention shows that, like its homologue ICAM-1, ICAM-2 can provided an imporant costimulatory signal during the TCR-mediated activation of CD4.sup.+ cells. The costimulatory signal during the TCR-mediated activation of CD4.sup.+ T cells. The costimulatory adhesion mediated by LFA-1:ICAM-2 interaction may provide a critical pathway for the initiation of T cell activation with ICAM-1.sup.- or ICAM-1.sup.low ICAM-2.sup.+ APC.